The research described in this competing renewal application for a Research Scientist Award (DA00101) is based on five research grants currently funded by NIDA and NIAAA. I am Scientific Director of a NIDA Clinical Research Center (DA 04059) concerned with Polydrug Abuse in Women and its biologic and behavioral consequences. Both cocaine and alcohol abuse disrupt menstrual cycle regularity and may result in amenorrhea, anovulation and luteal phase defects, as well as abnormalities of prolactin regulation. In pregnant women, alcohol and cocaine abuse increase the risk for spontaneous abortion, as well as congenital malformations and impaired neurobehavioral development in the neonate. Our studies of alcohol and cocaine abuse are directed towards clarifying ways in which acute and chronic drug exposure compromise regulation of the female neuroendocrine system. The neuroendocrine consequences of cocaine abuse are examined in women and in a primate model of cocaine self- administration. Parallel studies of the effects of alcohol on reproductive function in women and in a primate model of alcoholism are continuing (AAO4368, AAO6252). In clinical studies (DA 06116) we are continuing to evaluate the safety and effectiveness of buprenorphine for the treatment of polydrug abuse involving concurrent opiate and cocaine dependence and reduction of risk for HIV infection. Inpatient evaluations of the safety and effectiveness of buprenorphine are conducted on a Treatment Research Unit (TRU). Outpatient clinical trials are then conducted and buprenorphine has been approved for 52 weeks of treatment by the FDA. In related studies, the effectiveness of new medications for the treatment of cocaine abuse and polydrug abuse involving simultaneous cocaine and heroin abuse are being evaluated in a primate model. Preclinical studies of the behavioral pharmacology of buprenorphine are continuing (DA 02519). Buprenorphine significantly reduced cocaine self- administration in the primate model and current studies are examining the contribution of mu and kappa opiate receptor activity to cocaine- buprenorphine interactions. Analysis of the mechanisms of buprenorphine's effects on cocaine self-administration may suggest new directions for development of improved pharmacotherapies for drug abuse treatment. The overall objectives of the proposed research are to clarify the behavioral and biologic determinants and consequences of substance abuse and to improve understanding of the ways in which drugs act as reinforcers. Plans for professional growth include continued study of neuroendocrinology, brain imaging and computer science.